Liposomes are capsules which each composed of a lipid bilayer made of phospholipid and which have a size of several tens to hundreds of nanometers and can stably encapsulate a drug therein. One of the liposomes is a PEG liposome which is surface-modified with polyethylene glycol (PEG). The PEG liposome is inhibited from interacting with serum proteins such as opsonin and cells belonging to a monocytic cell line by a hydrated layer composed of surface PEG chains and the steric hindrance of the PEG chains and therefore can exhibit high retention in blood. In the delivery of anticancer drugs which require particularly high retention in blood, DOXIL®, which is a type of PEG liposome, is commercially available and has been proven in effectiveness.
On the other hand, in the delivery of nucleic acids such as siRNAs which have been intensively investigated in recent years, the PEG liposome is considered one of promising carriers. A siRNA is a nucleic acid drug inhibiting the production of pathogenic proteins, has few side effects, is advantageous in being readily synthesized in large quantities, and therefore is increasingly expected as a next-generation, high-performance drug. However, the siRNA is readily degraded by an internal enzyme in blood. Therefore, it is difficult to use the siRNA alone and a DDS technique for delivering the siRNA is essential. In the delivery of the siRNA using a liposome, an electrostatic complex with a nucleic acid is generally formed by adding an excessive amount of a cationic lipid to the liposome in order to stabilize the nucleic acid and the charge of the whole complex is cationized in order to increase the intake by cells.
One of components of the PEG liposome is phospholipid PEG, which contains a phosphoric group exhibiting anionicity and may possibly have negative influence on encapsulation depending on the type of a drug (Patent Literature 1 and Non Patent Literature 1). In particular, the phospholipid PEG is unsuitable for the encapsulation of a complex which contains the siRNA and which exhibits anionicity as a whole in some cases. Therefore, lipid PEG with no charge is attracting attention. It has been reported that when a liposome is composed of the lipid PEG, the liposome exhibits excellent stability and disposition (Non Patent Literature 2).    [Patent Literature 1] U.S. Pat. No. 6,586,001    [Non Patent Literature 1] THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, Vol. 328, No. 1, 321-330    [Non Patent Literature 2] Molecular Therapy, Vol. 17, No. 5, 872-879